The long-term goal of this project is to define the functional organization of the ventromedial frontal cortex and related structures such as the temporal and insular cortex, and the relation of these circuits to mood disorders. Previous work defined two distinct "orbital" and "medial" networks of interconnected areas within the orbital and medial prefrontal cortex (OMPFC). Differential connections to sensory and visceral control structures, and other observations, suggest that the orbital network is a sensory system related to food and reward, while the medial network is a viscero-motor system related to emotion. In humans, the OMPFC has been implicated in mood disorders and other psychiatric conditions but it is not known to what degree these differentially affect the two prefrontal networks. These neural circuits will be studied both in macaque monkeys and in humans. An ongoing neuroanatomical analysis in monkeys of the relation of the orbital and medial prefrontal networks with the temporal lobe with multiple anterograde and retrograde axonal tracers will be continued, and extended to include an analysis of the insula. In addition a new project is proposed to analyze pathways from the periaqueductal gray and the intralaminar nuclei of the thalamus to the OMPFC. In humans, a recently completed architectonic analysis of the OMPFC will be extended to an analysis of the temporal pole, temporal cortex and insula. The variability within the architectonic map of the OMPFC between different subjects or from side-to-side of the same brain will also be studied, using recently enhanced software to produce three-dimensional reconstructions and unfolded cortical maps. The role of OMPFC in mood disorders will be studied in two ways. First, previous observations of glial decreases in mood disorders will be extended to include additional brains obtained from the NIMH brain bank (in collaboration with Drs. Joel Kleineman and Wayne Drevets at NIMH), and to confirm recent data that oligodendrocytes are the major glial type affected. Second, activity patterns from functional imaging scans (PET and fMRI) from controls and mood disorder subjects will be analyzed in relation to the architectonic areas of the OMPFC (in collaboration with Dr. Drevets), to determine which specific areas and networks are affected in these disorders.